Focus on the Mechanisms and Functions of Pyroptosis, Inflammasomes, and Inflammatory Caspases in Infectious Diseases

Abstract

Eukaryotic cells can initiate several distinct self-destruction mechanisms to display essential roles for the homeostasis maintenance, development, and survival of an organism. Pyroptosis, a key response mode in innate immunity, also referred to as caspase-1-dependent proinflammatory programmed necrotic cell death activated by human caspase-1/4/5, or mouse caspase-1/11, plays indispensable roles in response to cytoplasmic insults and immune defense against infectious diseases. These inflammatory caspases are employed by the host to eliminate pathogen infections such as bacteria, viruses, protozoans, and fungi. Gasdermin D requires to be cleaved and activated by these inflammatory caspases to trigger the pyroptosis process. Physiological rupture of cells results in the release of proinflammatory cytokines, the alarmins IL-1β and IL-18, symbolizing the inflammatory potential of pyroptosis. Moreover, long noncoding RNAs play direct or indirect roles in the upstream of the pyroptosis trigger pathway. Here, we review in detail recently acquired insights into the central roles of inflammatory caspases, inflammasomes, and pyroptosis, as well as the crosstalk between pyroptosis and long noncoding RNAs in mediating infection immunity and pathogen clearance.

Pyroptosis and inflammasomes in diabetic wound healing

“…When germs, pathogens, or endotoxins stimulate cells, the caspase family becomes active, triggering pyroptosis, also known as inflammatory cell death. As a result of this process, cell swelling, cell membrane pore formation, cell membrane rupture, inflammasome activation, and finally the release of cell contents and inflammatory mediators all occur, culminating in severe inflammatory responses (11,12).…”

Relationship between pyroptosis-mediated inflammation and the pathogenesis of prostate disease

“…Prostatitis is an inflammatory disease that is linked to both infectious and non-infectious factors. Pyroptosis has turned out to be present in a variety of infectious and sterile diseases (60)(61)(62)(63)(64). The pyroptotic cells are able to promote the development of an inflammatory response by secreting the necessary cellular components and inflammatory mediators.…”

Molecular mechanisms and roles of pyroptosis in acute lung injury

“…[56] ALI resulting from infectious factors, such as bacteria, fungi, and viruses, has been demonstrated to be associated with AM pyroptosis. [57,58] On the one hand, pyroptosis of AMs is beneficial for resisting the invasion of different pathogens, and on the other hand, the release of plentiful inflammatory cytokines and the imbalance in the inflammatory response both amplify the inflammatory response, leading to the deterioration of ALI. [59] Thus far, it has been demonstrated that the specific mechanisms behind the induction of pyroptosis in macrophages vary from pathogen to pathogen.…”

“…AMs are essential for maintaining the stability of lung homeostasis and resisting invasion from the extrapulmonary environment, while IMs have an irreplaceable function in homeostasis regulation [56] . ALI resulting from infectious factors, such as bacteria, fungi, and viruses, has been demonstrated to be associated with AM pyroptosis [57,58] . On the one hand, pyroptosis of AMs is beneficial for resisting the invasion of different pathogens, and on the other hand, the release of plentiful inflammatory cytokines and the imbalance in the inflammatory response both amplify the inflammatory response, leading to the deterioration of ALI [59] …”

“…Thus far, it has been demonstrated that the specific mechanisms behind the induction of pyroptosis in macrophages vary from pathogen to pathogen. For example, Gram-negative bacteria such as Pseudomonas aeruginosa and Legionella pneumophila can initiate NLRC4- and caspase-11-dependent pyroptosis via flagellin and LPS, respectively, while coronavirus and certain fungi such as Candida albicans and Aspergillus fumigatus induce pyroptosis mainly through activating NLRP3 and AIM2 inflammasomes [57,58,60] . However, the stimulators that lead to macrophage pyroptosis are not limited to pathogens, and many other factors such as ion beams and lysosomal lysates, which are members of DAMPs, can also generate pyroptosis in macrophages [61] .…”